This Alzheimer's Disease Research Center proposal contains three specific core modules: 1) A Clinical Core which will recruit, evaluate and longitudinally follow and maintain a pool of AD patients for optimal care and clinical investigation and to serve potentially as subjects for autopsy. All will be included in a Dementia Registry and all data will be maintained in a central file. A protocol for quantitative nuclear magnetic resonance scans of AD patients for evaluation of its diagnostic utility is in- cluded. 2) The Tissue Specimen Core provides a coordinated neuropathological/neurochemical assessment facility on autopsy tissues for verification of AD for a variety of correlative clinical-biochemical-morphological research studies. 3) The Training and Information Core will provide research training to health professional students, postdoctoral fellows and faculty and continuing education to practitioners in the communities and state. To complement our AD Program Project Grant which will evaluate potential biochemical and morphological pathogenetic mechanisms in AD, one new RO-1 project is included in this proposal. It will investigate the role of calmodulin, calmodulin binding pro- teins and selected calmodulin regulated enzymes in AD brains, erythrocytes and leukocytes. We have attracted six new investigators from a broad spectrum of disciplines to perform pilot projects in AD. Proposed pilot studies include 1) investigation of the biochemical nature of neurofibrillary tangles, 2) alterations in genes on chromosome 21 in AD brains and lymphocytes, 3) evaluation at a cognitive retraining program for AD patients, 4) study of AD astrocytes' ability to express Ia antigen, produce IL-l and present antigen, 5) studies of coping capacities of AD families over time, 6) morphometric study of synaptic density correlated with senile plaque number in AD brain. All of the foregoing components are tied together by a strong administrative component. This component provides an administrative unit for day-to-day operations and leadership of the ADRC, an Executive Committee, a University-wide Advisory Committee to integrate the ADRC into existing University structures, and an External Advisory Committee to review proposed pilot projects and the ADRC itself. The University of Kentucky has provided significant new resources to support AD related activities at the Sanders-Brown Research Center.